Preventing radiocontrast-induced nephropathy in chronic kidney disease patients undergoing coronary angiography

Radiocontrast-induced nephropathy(RCIN) is an acute and severe complication after coronary angiography,particularly for patients with pre-existing chronic kidney disease(CKD).It has been associated with both short-and long-term adverse outcomes,including the need for renal replacement therapy,increased length of hospital stay,major cardiac adverse events,and mortality.RCIN is generally defined as an increase in serum creatinine concentration of 0.5 mg/dL or 25%above baseline within 48 h after contrast administration.There is no effective therapy once injury has occurred,therefore,prevention is the cornerstone for all patients at risk for acute kidney injury(AKI).There is a small but growing body of evidence that prevention of AKI is associated with a reduction in later adverse outcomes.The optimal strategy for preventing RCIN has not yet been established.This review discusses the principal risk factors for RCIN,evaluates and summarizes the evidence for RCIN prophylaxis,and proposes recommendations for preventing RCIN in CKD patients undergoing coronary angiography.     

Prophylaxis of contrast-induced nephropathy in patients undergoing coronary angiography.

Contrast-induced nephropathy (CIN) is a common complication of cardiac catheterization, reported to result in a 15% incidence of acute renal failure. Convincing evidence supports the prophylactic use of prehydration and low volumes of contrast medium. Recently, the antioxidant acetylcysteine has been shown to have a potential preventive role. The aim of this study was to examine the hypothesis that acetylcysteine prevents CIN. Patients undergoing cardiac catheterization with a serum creatinine >/= 1.5 mg/dl were prospectively randomized to receive acetylcysteine or placebo. A total of five doses of acetylcysteine 600 mg b.i.d. or placebo was administered, commencing on the day of the procedure. All patients were prehydrated with 0.45% saline and during the catheterization a nonionic low-osmolality contrast medium was used. Serum creatinine and urea were measured at 24, 48, and 72 hr postprocedure. A total of 43 patients were studied. There was no significant difference between the groups in terms of baseline characteristics, including baseline renal function. No adverse events were experienced with acetylcysteine treatment. Serum creatinine levels at 48 and 72 hr remained largely unchanged in the acetylcysteine group but continued to rise at 48 and 72 hr in the placebo group. By 72 hr, the incidence of CIN, defined as a 25% increase in baseline creatinine, was significantly lower in the acetylcysteine arm compared to placebo (5% for acetylcysteine vs. 32% for placebo; P = 0.046). In patients with mild to moderate renal impairment undergoing cardiac catheterization, prophylactic treatment with oral acetylcysteine reduces the incidence of contrast-induced nephropathy.     

Preventing contrast-induced nephropathy in patients with baseline renal dysfunction undergoing coronary angiography

Opinion statement  Although contrast-induced nephropathy (CIN) is usually self-limited, it may cause permanent renal injury and even lead to long-term dialysis in patients with preexisting renal impairment. Cardiologists face a dilemma as to whether to alleviate coronary syndromes by coronary intervention or to risk CIN in these patients. Strategies to prevent CIN, including hydration, use of low-osmolal or iso-osmolal contrast media, administration of N-acetylcysteine, and blood purification procedures, were proposed to be effective; however, there are conflicting results. Recently, we found that prophylactic hemodialysis could significantly improve renal survival in patients with advanced renal insufficiency undergoing coronary angiography in a randomized controlled trial. In these patients, fluid supplementation is poorly tolerated and impractical, especially in those with poor heart function. However, the routine use of prophylactic hemodialysis in patients with mild renal insufficiency requires further investigation.     

A new protocol using sodium bicarbonate for the prevention of contrast-induced nephropathy in patients undergoing coronary angiography

Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality rates. Although a previous study reported that pretreatment with sodium bicarbonate is more effective than sodium chloride for prophylaxis of CIN, this has not been a universal finding. We performed a prospective randomized trial to investigate whether CIN can be avoided using sodium bicarbonate. In total 155 patients with a glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) who were undergoing coronary angiography were enrolled. We assigned patients to sodium chloride plus sodium bicarbonate (bicarbonate group, n = 78) or sodium chloride alone (chloride group, n = 77). Infusion of sodium bicarbonate at 1 ml/kg/hour continued from 3 hours before to 6 hours after coronary angiography. CIN was defined as a 25% increase in serum creatinine from baseline value or an absolute increase of ≥0.5 mg/dl, which appeared within 2 days of contrast. Baseline GFR was not significantly different between the 2 groups. Patients in the bicarbonate group had a higher GFR than those in the chloride group on day 2 (45.8 ± 13.4 vs 40.9 ± 14.6 ml/min/1.73 m(2), p = 0.031) and at 1 month (49.5 ± 14.7 vs 43.7 ± 15.5 ml/min/1.73 m(2), p = 0.019). CIN occurred in 10 patients (13%) in the chloride group but in only 2 patients (2.6%) in the bicarbonate group (p = 0.012). Sodium chloride plus sodium bicarbonate is more effective than sodium chloride alone for prophylaxis of CIN and can lead to retention of better long-term renal function.     

Comparison of usefulness of sodium bicarbonate versus sodium chloride to prevent contrast-induced nephropathy in patients undergoing an emergent coronary procedure

In the case of an emergency coronary procedure where the risk of contrast-induced nephropathy is especially high, there are few reliable methods to attenuate renal injury. We examined the efficacy of sodium bicarbonate for the prevention of contrast-induced nephropathy in patients undergoing an emergency coronary procedure. We enrolled 59 patients who were scheduled to undergo an emergency coronary angiography or intervention. These patients were randomized to receive a 154-mEq/L infusion of sodium bicarbonate (n = 30) or sodium chloride (n = 29), as a bolus of 3 ml/kg/hour for 1 hour before the administration of contrast, followed by an infusion of 1 ml/kg/hour for 6 hours during and after the procedure. In the sodium bicarbonate group, serum creatinine concentration remained unchanged within 2 days of contrast administration (1.31 +/- 0.52 to 1.31 +/- 0.59 mg/dl), whereas it increased in the sodium chloride group (1.32 +/- 0.65 to 1.52 +/- 0.92 mg/dl, p = 0.01). The incidence of contrast-induced nephropathy (an increase >0.5 mg/dl or >25% in serum creatinine concentration within 2 days of contrast) was significantly lower in the sodium bicarbonate group than in the sodium chloride group (7% vs 35%, p = 0.01, risk ratio 0.19, 95% confidence interval 0.046 to 0.80). In conclusion, hydration with sodium bicarbonate is more effective than with sodium chloride for the prevention of contrast-induced nephropathy in patients undergoing an emergency coronary procedure.     

The prevention of contrast-induced nephropathy in patients undergoing percutaneous coronary intervention

Contrast-induced nephropathy (CIN) is a leading cause of morbidity and mortality in high-risk patients undergoing percutaneous coronary intervention (PCI) or other radiocontrast procedures. Approximately 25% of all patients selected for these procedures are at risk for its development. Patients who experience this complication have higher rates of mortality, longer hospital stays and poorer long-term outcomes. The occurrence of CIN is directly related to the number of co-existing clinical risk factors. Among the many risk factors, preexisting renal impairment, advanced age, the presence of diabetes mellitus and both the volume and type of the contrast agent administered are among the most important. While the precise pathophysiological mechanisms responsible for this condition are complex and incompletely understood, experimental studies suggest that the pathogenesis involves a combination of renal ischemia and direct tubular epithelial cell toxicity. At the present time, adequate periprocedural hydration and the selection of low-osmolar and, more recently, iso-osmolar contrasts agents are the only available tools to the operator for reducing the risk of this complication. Several other modalities, such as the use of NaHCO3 and hemofiltration, also appear promising in preventing the development of this complication. This article reviews the epidemiology, pathophysiology, and consequences of CIN. It also reviews the risk factors for the development of CIN, as well as the history of the various modalities studied in its prevention.     

Acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography

Background

Contrast-induced nephropathy (CIN) after coronary angiography is associated with increased morbidity and mortality rates. Preliminary studies with N-acetylcysteine (NAC) have found conflicting results in the prevention of CIN in patients undergoing coronary angiography. This study was designed to evaluate the efficacy and safety of NAC in the prevention of CIN in patients undergoing coronary angiography.

Methods

This study was prospective, randomized, double-blind, and placebo-controlled. Patients referred for elective coronary angiography with a baseline creatinine clearance level <50 mL/min and serum creatinine >1.2 mg/dL were randomly assigned to 1500 mg NAC or placebo, starting the evening before angiography and given every 12 hours for 4 doses. The primary study end point was the development of CIN, which was defined as an increase of >0.5 mg/dL or an increase of ≥25% in serum creatinine over baseline within 48 hours of angiography. Secondary end points included changes in serum creatinine and blood urea nitrogen, requirement of dialysis, side effects of study medication, hospital length of stay, and hospital charges.

Results

CIN occurred in 8.2% (4/49) of patients taking NAC and 6.4% (3/47) of patients taking placebo. Changes in BUN and serum creatinine from baseline were not significantly different in the two treatment groups. Baseline BUN and volume of contrast were the only independent predictors of CIN. More patients with diabetes had development of CIN (5/43; 12%) compared with nondiabetic patients (2/52; 4%), but the difference was not significant (P = .15). The incidence of CIN in diabetic patients was not different in the two treatment groups. No patient with development of CIN required dialysis. Side effects (mostly gastrointestinal) occurred in 16% of patients taking NAC and in none of the patients taking placebo. Length of stay and hospital charges were not different between the treatment groups.

Conclusions

In patients with reduced renal function undergoing elective coronary angiography, NAC does not reduce the risk of CIN.     

Prevention of contrast-induced nephropathy by bolus injection of sodium bicarbonate in patients with chronic kidney disease undergoing emergent coronary procedures

We conducted a prospective study to determine whether a bolus injection of sodium bicarbonate before emergent coronary procedures in patients with chronic kidney disease (CKD) might prevent contrast-induced nephropathy (CIN). We enrolled 59 patients with CKD, defined by a serum creatinine concentration of >1.1 mg/dl or an estimated glomerular filtration rate of <60 ml/min, who were scheduled at admission to undergo an emergent coronary procedure. The patients were randomized to receive a bolus intravenous injection of 154 mEq/L of sodium bicarbonate (n = 30) or sodium chloride (n = 29) at the dose of 0.5 ml/kg, before contrast administration, followed by infusion of 154 mEq/L sodium bicarbonate at 1 ml/kg/hour for 6 hours in both groups. The primary end point was the occurrence of CIN, defined as an increase by > 25% or > 0.5 mg/dl of the serum creatinine level within 2 days after the procedure. In the sodium bicarbonate group, the serum creatinine concentration remained unchanged within 2 days of contrast administration (from 1.32 ± 0.46 to 1.38 ± 0.60 mg/dl, p = 0.33). In contrast, it had increased in the sodium chloride group (1.51 ± 0.59 to 1.91 ± 1.19 mg/dl, p = 0.006). The incidence of CIN was significantly lower in the sodium bicarbonate group than in the sodium chloride group (3.3% vs 27.6%, p = 0.01). In conclusion, rapid alkalization by bolus injection of sodium bicarbonate was effective for the prevention of CIN in patients with CKD undergoing emergent procedures.     

Higher hydration volume may not reduce the risk of contrast-induced nephropathy in patients with chronic kidney disease undergoing percutaneous coronary intervention

Background Adequate hydration with isotonic saline is generally recommended to prevent contrast-induced nephropathy(CIN) in patients with chronic kidney disease(CKD). However, there is no well-defined protocol regarding the optimal rate and duration of normal saline administration. Methods Patients with CKD(estimated glomerular filtration rate [e GFR] 60 m L/min/1.73 m2) undergoing PCI with hydration at the speed recommended by the current guidelines(1 m L/kg/h [0.5 ml/kg/h for left ventricular ejection fraction 40% or severe congestive heart failure]) were included in the study(n=631). CIN was defined as an increase in serum creatinine of ≥0.5 mg/d L or 25% from the baseline within 48-72 hours after contrast exposure. Results Individuals with higher adequate hydration(HV/W ratios) were more likely to develop CIN(Q1, Q2, Q3, and Q4: 6.33%, 18.4%,12.5%, and 21.52%, respectively; P=0.001), acute heart failure(5.7%, 6.13%, 9.21%, and 13.92%, respectively;P=0.035). Multivariate analyses showed that higher hydration volume was not significantly associated with a reduced risk of CIN(HV/W ratio Q2 vs. Q1: odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.08~5.16; Q3 vs. Q1: OR: 1.47, 95% CI: 0.63~3.4; Q4 vs. Q1: OR: 2.32, 95% CI: 1.05~5.11). Conclusion Higher hydration volume may not reduce the risk of contrast-induced nephropathy in patients with CKD undergoing PCI.intravascular hydration volume at routine speed may not decrease the risk of CIN in patients with chronic kidney disease undergoing percutaneous coronary intervention.     

严重肾功能不全患者冠状动脉介入治疗后行血液滤过预防对比剂肾病的发生

目的评估严重肾功能不全患者冠状动脉介入治疗后行床旁血液滤过对对比剂肾病（CIN）的发生率及临床疗效的影响。方法回顾性分析本中心30例因严重肾功能不全行冠状动脉介入治疗的患者,术后即刻给予床旁血液滤过,收集临床资料,检测患者术前和术后24 h、72 h、1周的肌酸酐（肌酐）值,并根据Cockcroft和Gault equation公式计算肌酐清除率（CrCl）,评估术后CIN发生率,以及短期临床疗效。结果 30例患者平均年龄（729±8.7）岁,其中男21例（70.0%）。慢性肾疾病分期（CKD）3期3例（10.0%）,CKD 4期20例（66.7%）,CKD 5期7例（23.3%）;平均血液滤过持续时间（7.5±4.1）h,术前和术后24 h、72 h、1周血肌酐值分别为（498.7±143.7）、（353.2±128.0）、（450.0±132.2）、（488.0±145.7）μmol/L,CrCl值分别为（20.3±10.2）、（36.5±14.3）、（28.3±10.4）、（21.0±10.3）ml/min,患者术后未出现CIN。平均随访（3.1±2.6）个月,30例患者未见新发心血管事件,且未见新发需依赖血液透析患者。结论对于严重肾功能不全的患者,介入治疗后行床旁血液滤过可以减少对比剂肾病的发生,是一个可供选择的减少对比剂肾病的预防措施。     

老年慢性肾功能不全患者冠状动脉介入治疗中连续性静静脉血液滤过预防对比剂肾病的效果

目的 观察和分析连续性静静脉血液过滤(continuous venovenous hemofiltration,CVVH)对老年肾功能不全患者行冠状动脉介入（PCI）治疗期间发生对比剂肾病（CIN）的预防效果。方法 回顾性分析我院60例肾功能不全行PCI的老年患者,按治疗肾功能不全的方法分为CVVH组（30例）与常规水化组（30例）。CVVH组术前4 h及术后18 h给予CVVH,常规水化组术前12 h及术后12 h给予生理盐水。检测两组患者术前和术后即刻、24 h、72 h和1 周的血肌酐,比较两组术后CIN的发生率。并随防6个月,观察和分析进入持续血透、非死亡心血管事件和死亡发生率。结果 两组患者临床特点无显著差异,PCI手术情况无显著差异。两组术后即刻、24 h、72 h和1周血肌酐比较有显著差异（P<0.05,P<0.01）。CVVH组CIN发生率7%,常规水化组30%,两组相比差异显著（P<0.05）。随访（5.6±1.2）个月,CVVH组需维持血透1例、常规水化组7例,CVVH组新发心血管事件1例,常规水化组6例,均有显著差异(P<0.05)。两组分别死亡1例和2例,病死率无显著差异。结论 对于老年肾功能不全的冠心病患者,PCI前后行CVVH可以显著减少CIN、维持血透及心血管事件的发生率。     

尿pH值与慢性肾脏疾病患者对比剂肾病的关系

目的 探讨尿pH值与慢性肾脏疾病（chronic kidney disease,CKD）患者经皮冠状动脉介入（percutaneous coronary intervention,PCI）治疗或冠状动脉造影术（coronary angiography,CAG）后对比剂肾病（contrast-induced nephropathy,CIN）的相关性.方法 回顾性分析2009年9月至2012年8月在广东省人民医院行择期PCI治疗或CAG的CKD患者453例的临床资料.按术前尿pH值水平将患者分为2组：尿pH值≥6组（n=254例）,尿pH值＜6组（n=199例）.比较两组之间的基线资料、CIN发病率、院内病死率及血液透析率.采用单因素Logistic 回归分析筛选CIN的危险因素,采用多因素Logistic回归分析尿pH值＜6与CIN的关系.结果 共52例患者（11.5％）发生CIN;尿pH值≥6组,尿pH值＜6组CIN的发病率分别5.5％ （14/254）、19.1％（38/199）,两组比较差异有统计学意义（P＜0.001）;院内病死率分别为0和1.5％ （3/199）,两组比较差异无统计学意义（P=0.050）;血液透析率分别为0.4％（1/254）和1.5％（3/199）,两组比较差异无统计学意义（P=0.209）.单因素Logistic回归分析显示,尿pH值＜6与CIN的发病率相关（OR =4.406,95％CI：2.124-7.708,P＜0.001）;多因素Logistic回归分析提示,尿pH值＜6是CIN的独立危险因素（OR =3.267,95％CI：1.674-6.374,P=0.001）.结论 CKD患者术前尿pH值＜6与择期PCI或CAG术后CIN相关,尿pH值＜6增加发生CIN的风险.     

造影剂温度对经皮冠状动脉介入治疗患者造影剂肾病发病率的影响

目的 探讨造影剂温度对造影剂肾病（CIN）发病率的影响。方法 将157例经皮冠状动脉介入（PCI）治疗患者随机分为20℃碘克沙醇组（20℃组,n=77）和37℃碘克沙醇组（37℃组,n=80）。 分别于PCI术前、后行血液流变学指标检测;PCI术前24 h内、术后12、24 和48 h检测血浆胱抑素C和肌酐。分析两种温度造影剂对患者肾功能和血液流变学指标的影响。结果 20℃组PCI术后24 h的胱抑素C、48 h的肌酐显著高于术前(P<0.05),全血高切、低切表观黏度亦显著较术前升高,差异有统计学意义（P<0.05）。 37℃组PCI术后24 h的胱抑素C、48 h的肌酐低于20℃组相应时间点水平,且PCI术后全血高切、低切表观黏度亦低于术后20℃组,具有统计学意义（P<0.05）。37℃组CIN发生率（2%）显著低于20℃组（8%）,具有统计学意义（P<0.05）。结论 37℃碘克沙醇的CIN发生率显著低于20℃碘克沙醇。     

Hyperuricemia as a risk factor for contrast-induced nephropathy in patients with chronic kidney disease.

OBJECTIVES: Hyperuricemia as a risk factor for contrast-induced nephropathy (CIN) has not been studied. BACKGROUND: The aim of the present study was to assess the influence of hyperuricemia on the development of CIN in patients undergoing coronary angiography. METHODS: This was a prospective cohort study. A total of 266 patients with a mean age of 58.33 +/- 7.85 years and serum creatinine > or = 1.2 mg/dl were divided into two groups (hyperuricemic, n = 126, and normouricemic, n = 140). CIN was defined as an increase of > or = 25% in creatinine over baseline within 48 hr of angiography, and hyperuricemia as serum uric acid > or = 7 mg/dl in males and > or = 6.5 mg/dl in females. RESULTS: CIN occurred in 15.1% of the hyperuricemic group and 2.9% of the normouricemic group (P < 0.001). Serum creatinine increased from 1.45 +/- 0.20 to 1.67 +/- 0.45 mg/dl in the hyperuricemic group and from 1.42 +/- 0.16 to 1.56 +/- 0.23 mg/dl in the normouricemic group (P < 0.001). Hyperuricemia [odds ratio (OR) 4.71; 95% confidence interval (95% CI) 1.29-17.21; P = 0.019] and a high incidence of multi-vessel coronary involvement (OR 3.59; 95% CI 1.12-11.48; P = 0.032) in the hyperuricemic group were predictors of CIN. Hypoalbuminemia (P = 0.001) and age > or = 70 years (P = 0.023) were other risk indicators of CIN. Length of hospital stay (P < 0.001) and CIN requiring renal replacement therapy (P = 0.017) were significantly higher in hyperuricemic group. Serum uric acid level > or = 7 mg/dl in males and > or = 5.9 mg/dl in females were found to be the best cut-off value for prediction of CIN. CONCLUSION: Our data support the hypothesis that patients with hyperuricemia are at risk of developing CIN.     

Comparison of contrast-induced nephrotoxicity of iodixanol and iopromide in patients with renal insufficiency undergoing coronary angiography

This prospective, randomized, double-blind study was performed to compare the incidence of contrast-induced nephropathy (CIN) after the administration of the iso-osmolar contrast medium iodixanol to the low-osmolar contrast medium iopromide during coronary angiography in patients with impaired renal function. Patients with creatinine clearance (CrCl) <60 ml/min who underwent coronary angiography and/or percutaneous coronary intervention were randomized to receive either iodixanol (n = 215) or iopromide (n = 205). The primary study end point was the incidence of CIN, which was defined as an absolute increase in serum creatinine (SCr) ≥0.5 mg/dl (44.2 mol/L) or a relative increase ≥25% compared to baseline SCr. The secondary end points were the proportion of patients with increases in SCr ≥0.5 mg/dl, the proportion with SCr increases ≥1.0 mg/dl (88.4 mol/L), and the peak increase in SCr. Age, the presence of diabetes mellitus, mean baseline SCr, CrCl, the use of N-acetylcysteine, contrast volume, and the predicted risk score for CIN were similar in the 2 groups. CIN developed in 39 patients (9.3%); there was no significant difference between the iodixanol and iopromide groups (10.7% and 7.8%, respectively; absolute difference 2.9%, 95% confidence interval -3.1% to 8.9%, p = 0.394). The proportions of patients with SCr increases ≥0.5 mg/dl (6.5% vs 6.3%) and ≥1.0 mg/dl (2.8% vs 2.9%) were similar in the 2 groups. There was a tendency for more patients with relative increases ≥25% (10.2% vs 6.8%) and greater peak increases in SCr (0.037 ± 0.375 vs 0.029 ± 0.351 mg/dl) to be in the iodixanol group, but these differences were not statistically significant. In conclusion, the incidences of CIN after coronary angiography did not significantly differ between the iodixanol and iopromide groups in patients with impaired renal function.